In 2371, the Monitor was assigned a covert mission to destroy the Borg Homeworld, fitted with a Transwarp drive and command was temporarily handed over to AmbassadorSpock, accompanied by the senior staff of the recently-destroyed USS Enterprise-D, the visiting Admiral Leonard McCoy and the recently-resurrected Captain James T. Kirk. Before departing on the mission, Captain Lewinski had the name "USS Enterprise" painted on her hull as a tribute to her new temporary crew.

The ship reached the Borg Homeworld in the Delta Quadrant where it engaged a joint Romulan-Borg armada, destroying the Romulan Flagship IRW Avatar of Tomed. The Enterprise discovered the Central Node of the Borg Collective; although the Enterprise was too damaged to destroy it with its currently-disabled weapons, Kirk apparently sacrificed himself to destroy the Node and therefore severed the connections of the entire Collective, leaving them reduced to smaller 'components' who would be more vulnerable in future. With their mission accomplished, the Enterprise then headed back to the Alpha Quadrant.

In 2375, the Monitor was lost with all hands while conducting tests on her transwarp drive traveling between Starbases324 and 718 with a skeleton crew of thirty-eight, twenty of whom were warp engineers/specialists. While conducting the tests the Monitor was swept into Intra-galactic space between the Milky Way and AndromedaGalaxies, 350,000 light-years from the Milky Way with an inoperative Transwarp drive and a centuries long return trip home, at warp speeds, ahead of them.